title: CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells.
abstract: Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.
authors.affiliation: Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710061, PR China.
authors.forename: Tian Jun
authors.initials: TJ
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.forename: Asmitanand
authors.initials: A
authors.lastname: Thakur
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Ming Wei
authors.initials: MW
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C546534:CACUL1 protein, human; D044842:Cullin Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CDK-associated Cullin 1; Cell cycle; Lung cancer; Mitogen-activated protein kinases; Proliferation